RRC ID 57225
Author Colmenares SU, Swenson JM, Langley SA, Kennedy C, Costes SV, Karpen GH.
Title Drosophila Histone Demethylase KDM4A Has Enzymatic and Non-enzymatic Roles in Controlling Heterochromatin Integrity.
Journal Dev Cell
Abstract Eukaryotic genomes are broadly divided between gene-rich euchromatin and the highly repetitive heterochromatin domain, which is enriched for proteins critical for genome stability and transcriptional silencing. This study shows that Drosophila KDM4A (dKDM4A), previously characterized as a euchromatic histone H3 K36 demethylase and transcriptional regulator, predominantly localizes to heterochromatin and regulates heterochromatin position-effect variegation (PEV), organization of repetitive DNAs, and DNA repair. We demonstrate that dKDM4A demethylase activity is dispensable for PEV. In contrast, dKDM4A enzymatic activity is required to relocate heterochromatic double-strand breaks outside the domain, as well as for organismal survival when DNA repair is compromised. Finally, DNA damage triggers dKDM4A-dependent changes in the levels of H3K56me3, suggesting that dKDM4A demethylates this heterochromatic mark to facilitate repair. We conclude that dKDM4A, in addition to its previously characterized role in euchromatin, utilizes both enzymatic and structural mechanisms to regulate heterochromatin organization and functions.
Volume 42(2)
Pages 156-169.e5
Published 2017-7-24
DOI 10.1016/j.devcel.2017.06.014
PII S1534-5807(17)30502-6
PMID 28743002
PMC PMC5572651
MeSH Animals Biocatalysis Cell Cycle / genetics Cell Cycle Checkpoints / genetics Chromosomal Position Effects / genetics DNA Breaks, Double-Stranded DNA Repair / genetics Drosophila Proteins / chemistry Drosophila Proteins / metabolism* Drosophila melanogaster / cytology* Drosophila melanogaster / enzymology* Drosophila melanogaster / genetics Fertility / genetics Gene Expression Regulation Gene Silencing Heterochromatin / metabolism* Histone Demethylases / metabolism* Histones / metabolism Lysine / metabolism Methylation Mutation / genetics Protein Domains Transcription, Genetic
IF 9.19
Times Cited 17